Differential effect of FasL on GvHD disease according to its source

Objective: Hematopoietic stem cell transplantation is a potentially curative treatment for hematologic malignancies. An important limitation of its use is the frequent occurrence of graft versus host disease (GvHD). GvHD is associated with complex interactions between innate and adaptive immunity. The incidence of GvHD is 40 to 80% depending on donor-and transplant-characteristics. A number of pathways have been described on allogeneic T cell-mediated cytotoxicity, including the Fas/Fas ligand (FasL) pathway. However, the overall mechanistic findings on how FasL expression in donor cells affects target tissues remains poorly characterized. Methods: We used a well-defined CD4 and CD8-dependent sclerodermatous GvHD model. GvHD is induced by transplantation of low doses of T-and B-cell depleted BM cells and splenocytes from C57BL/6 mice into lethally irradiated BALB/c mice. Colon and skin samples were analyzed by flux cytometry and HE suggesting a regulatory environment. Conclusion: These results indicate that FasL expression, either in BM or in in splenocytes, acts differentially in GvHD. FasL expression by donor myeloid cells confers protection from aGvHD via the production of IL-18. In contrast, FasL expression by donor T cells mediates cytotoxicity.